An Injectable Hydrogel Composing Anti-Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment...

Area of Science:

• Biomaterials Science
• Rheumatology
• Regenerative Medicine

Background:

• Rheumatoid arthritis (RA) presents significant challenges for bone erosion healing due to persistent inflammation, excessive osteoclast activity, and compromised osteoblast function.
• Current biomaterial strategies often fall short in addressing the complex osteoimmune and osteogenic dysregulation characteristic of RA bone erosion.
• A novel approach is required to engineer the microenvironment for effective bone regeneration in RA patients.

Purpose of the Study:

• To develop an in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel for remodeling the osteoimmune and osteogenic microenvironment of bone erosion healing in rheumatoid arthritis.
• To engineer a multi-stage drug delivery platform integrated within the IPN hydrogel for controlled release of therapeutic agents.
• To evaluate the efficacy of the developed bioactive IPN hydrogel in promoting bone reconstruction in a preclinical model of rheumatoid arthritis.

Main Methods:

• An injectable IPN hydrogel was synthesized using a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, combined with electrostatic interactions involving bisphosphonate-functionalized HA (HABP) and zinc (Zn)-doped biphasic calcium phosphate (ZnBCP) nanorods.
• The IPN hydrogel's adaptability to irregular bone defect shapes and its capacity for multi-stage release of therapeutic ions (calcium, phosphate, Zn) were characterized.
• The hydrogel's effects on osteoimmune cells (promoting M2 macrophages, inhibiting osteoclasts) and osteogenic differentiation were assessed in vitro and in vivo using a collagen-induced arthritis rabbit model.

Main Results:

• The developed IPN hydrogel demonstrated excellent in situ adaptability and injectability, conforming to complex bone erosion geometries.
• Integration of ZnBCP and HABP enabled controlled, multi-stage release of ions, effectively modulating the inflammatory response by promoting anti-inflammatory M2 cells and suppressing osteoclast activity.
• Sustained co-delivery of calcium and phosphate ions, along with zinc, significantly enhanced osteogenic properties, promoting osteoblast differentiation and bone formation.
• The bioactive IPN hydrogel therapy successfully remodeled the osteoimmune environment, exhibiting synergistic pro-inflammation-resolving, osteogenesis-promoting, and anti-osteoclastic activities.

Conclusions:

• The novel bioactive IPN hydrogel effectively addresses the challenges of bone erosion healing in rheumatoid arthritis by creating a conducive microenvironment.
• This therapeutic strategy demonstrates significant potential for bone reconstruction by simultaneously resolving inflammation, promoting osteogenesis, and inhibiting osteoclast-driven bone resorption.
• The findings highlight the promise of this engineered hydrogel platform for regenerative medicine applications in inflammatory bone diseases.